Various proteinaceous components of bone and dentin have been identified. Some of those components, such as collagen, are major structural components and are also present in soft tissues of the body. Noncollagenous proteins (10%) may play functional roles specific to bone and dentin, such as initiation of mineralization and control of calcium phosphate crystal growth and degradation (Glimcher, in Disorders of Bone and Mineral Metabolism, Coe et al., eds., Raven Press, New York, 1992, p. 265-288; Young et al., in Cellular and Molecular Biology of Bone, Noda, ed., Academic Press, San Diego, 1993, p. 191-234; Heinegard et al., FASEB J. 2:2041-51, 1989; Delmas et al., Calcif. Tissue Int. 36:308-16, 1983). Major noncollagenous extracellular matrix proteins include osteocalcin, osteonectin, osteopontin, bone sialoprotein, decorin, and biglycan (Glimcher, 1992, supra; Young et al., 1993, supra,; Heinegard et al., 1989, FASEB J. 2, 2041-51). Common clinically used bone markers include osteocalcin, type I collagen, pyridinoline, dexoxypyridinoline, and alkaline phosphatase (Delmas, 1993, in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Favus, ed., 2nd Ed., Lippincott-Raven Publishers, Philadelphia).
In some contexts, it is desirable to distinguish bone from soft tissue. Specificity of bone markers may be reduced if the marker is also expressed in soft tissue or if antibodies to it react with moieties found in soft tissue, including fragments or degradation products of a marker specifically expressed in bone. For example, while osteocalcin is bone-specific, some osteocalcin antibodies have been shown to also react to some extent with matrix Gla-containing protein, which is distributed in many soft tissues in addition to bone (Hauschka et al., 1989, Physiol. Rev. 69, 990-1047)..sup.1 Osteocalcin protein fragments are also present in blood because of bone resorption. Thus, serum osteocalcin levels may not reflect bone formation. In addition, because most osteocalcin is excreted from kidney, osteocalcin levels in individuals with kidney diseases may not accurately reveal the state of bone metabolism. FNT .sup.1 The abbreviations used are: BSA, bovine serum albumin; Fc.alpha.R, Fc receptor for Ig; Gdn, guanidine; Gla, carboxyglutamic acid; HPLC, high performance liquid chromatography; Ig, immunoglobulin; Mab, monoclonal antibody; PAGE, SDS-polyacrylamide gel electrophoresis; PCR, polymerase chain reaction; RT, reverse transcriptase; RP, reversed phase.